title: Effects of ageing, prolonged estrogen deficiency and zoledronate on bone tissue mineral distribution.
abstract: The quantity and distribution of bone tissue mineral are key determinants of bone strength. Recent research revealed altered mineral distribution within sheep femora following estrogen deficiency. Rapid increases in bone remodeling occur at the onset of estrogen deficiency and abate over time. Therefore, altered tissue mineralization might be a transient characteristic of osteoporosis. Bisphosphonates reduce fracture incidence by 40-60% but increases in bone mineral density are insufficient to explain such changes. In this study the hypotheses that bone tissue mineralization is altered over prolonged estrogen depletion and bisphosphonate treatment were tested. Quantitative backscattered imaging (qBEI) was used to quantify bone mineral density distribution (BMDD) parameters (mean, FWHM) in trabeculae from the proximal femora of an ovariectomized sheep model that underwent estrogen deficiency for 31 months, an ovariectomized group administered with Zoledronic acid and age-matched controls. To assess the effects of normal ageing and prolonged estrogen deficiency, data were compared to BMDD data from sheep that were estrogen deficient for 12 months and age-matched controls. This study reports that normal ageing increases mean mineralization and mineral heterogeneity at a trabecular level. In contrast, prolonged estrogen deficiency leads to significantly decreased mean mineralization and further exacerbates increases in mineral heterogeneity. Interestingly, ZOL treatment of OVX sheep significantly reduced tissue mineral variability, both at a trabecular level and between femoral regions. Together, these findings indicate that ZOL treatment acts to reverse the increased mineral heterogeneity occurring during estrogen deficiency, which may contribute to its capacity to reduce osteoporotic fractures.
authors.affiliation: Biomechanics Research Centre (BMEC), Department of Mechanical and Biomedical Engineering, National University of Ireland, Galway, Ireland; Bioengineering Sciences Research Group, Faculty of Engineering and the Environment, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Brennan
authors.forename: J P
authors.initials: JP
authors.lastname: Gleeson
authors.forename: F J
authors.initials: FJ
authors.lastname: O'Brien
authors.forename: L M
authors.initials: LM
authors.lastname: McNamara
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004967:Estrogens / Q000172:deficiency*; D005269:Femur / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D012756:Sheep; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004967:Estrogens; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: BMDD; Heterogeneity; Mineralization; Osteoporosis; Trabeculae; Zoledronic acid